New Inotropic Pharmacologic Strategies Targeting the Failing Myocardiumin the Newborn and Infant

Abstract

Pharmacologic support of the failing neonatal heart to maintain cardiac output, which is vital for sufficient end organ perfusion, is a challenging task for the pediatric intensivist, especially since strategies which have been proven to be effective in adults cannot necessarily be extrapolated to neonates. The unique biochemical properties and structure of the neonatal heart, including the increased non-contractile tissue mass, a lower responsiveness to beta adrenergic agents and the heart rate dependent cardiac output with a limited ability to increase stroke volume, favor some of the new inotropes of the Ca+ sensitizer family. Focusing on the after load reduction, inodilators as phosphodiesterase inhibitors and human brain natriuretic peptide offer treatment options for the neonatal myocardium. Additionally, thyroxine and steroids have been investigated in neonates with low cardiac output after surgery for congenital heart disease. Gene therapy, in particular cardiac-selective gene transfer, might offer perspectives for future support for the neonatal heart. This text reviews some of the most recent pharmacologic strategies targeting the failing myocardium in the critically ill newborn and infant.

Using adrenaline during neonatal resuscitation may have an impact on serum cardiac troponin-T levels

“…The newborn heart has a greater volume of noncontractile myocardial tissue mass than later in life and has a limited capacity to increase stroke volume. Neonatal cardiac output is therefore more dependent on heart rate, and it has been suggested that it is more vulnerable to apoptosis (28). Muontaldo et al found that when cardiac involvement occurred during asphyxia, a worse neurodevelopmental outcome could be expected.…”

Isoproterenol stimulates 5′-AMP-activated protein kinase and fatty acid oxidation in neonatal hearts

“…However, in the presence of physiological concentrations of palmitate (0.4 mM), the rates of cardiac glucose oxidation are markedly inhibited in the early neonatal period, due to low-PDH activity (43). Despite possessing the capacity to readily oxidize glucose, the contribution of glucose oxidation to cardiac ATP generation only increases marginally in the fatty acid-perfused neonatal heart and does not fully mature until weaning (35).Pharmacological support with inotropic agents is an important, clinically utilized intervention for the management of impaired cardiac contractile function (60,73). A hallmark response of the myocardium to inotropic/chronotropic stimulation is an increase in oxygen consumption (MV O 2 ); however, the effects of catecholamines on AMPK and ACC are complex.…”

“…Pharmacological support with inotropic agents is an important, clinically utilized intervention for the management of impaired cardiac contractile function (60,73). A hallmark response of the myocardium to inotropic/chronotropic stimulation is an increase in oxygen consumption (MV O 2 ); however, the effects of catecholamines on AMPK and ACC are complex.…”